Altered distribution and co-localization of polycystin-2 with polycystin-1 in MDCK cells after wounding stress

被引:16
作者
Scheffers, MS
van der Bent, P
van de Wal, A
van Eendenburg, J
Breuning, MH
de Heer, E
Peters, DJM
机构
[1] Leiden Univ, Med Ctr, Dept Human Genet, Ctr Human & Clin Genet,Sylvius Lab, NL-2333 AL Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Pathol, NL-2333 AL Leiden, Netherlands
关键词
ADPKD; polycystin-1; polycystin-2; co-localization; MDCK; wound healing;
D O I
10.1016/j.yexcr.2003.08.019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Polycystin-1 and -2 are integral membrane glycoproteins defective in autosomal dominant polycystic kidney disease (ADPKD). Recent studies showed a coupled polycystin-land -2 action in cell signaling and channel activation suggesting an important biological role for the two proteins at the plasma membrane. To gain a better understanding about the (co)-distribution and dynamics of the polycystin-1 and -2 complex under stress conditions, we used a wound-healing model of Madine Darby canine kidney (MDCK) renal epithelial cells. In this model, cells near the wound edge undergo a process of reorganization to active migration, while cells further from the edge are unaffected and remain confluent. For the first time, endogenous polycystin-1 and -2 were found to partly co-localize in the plasma membrane of confluent monolayers, and both proteins co-localized in the primary cilium. Upon wound healing, the association of polycystin-2 to the membrane was greatly reduced at the wound edge and the submarginal cells. Polycystin-1 remained incorporated to the membrane at the edge of the cell sheet at all time points, although strongly reduced in lamellipodia-forming cells. Adherens junctions and desmosomes, and respective connected actin and keratin cytoskeleton were also disturbed in lamellipodia-forming cells. We propose that altered subcellular localization of polycystin-1 and -2 as a result of stress will affect signaling and other cellular processes mediated by these proteins. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:219 / 230
页数:12
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